Effect of Glucagon on Cyclic 3′,5′-AMP, Phosphorylase Activity and Contractility of Heart Muscle of the Rat

The purpose of this investigation was to contrast the effect of glucagon and that of epinephrine on the concentration of cyclic adenosine 3′,5′-monophosphate (cyclic AMP), the activity of phosphorylase a and the contractile amplitude of isolated perfused rat hearts. The two drugs were about equally...

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Bibliographic Details
Published in:Circulation research 1970-02, Vol.26 (2), p.225-233
Main Authors: MAYER, STEVEN E, NAMM, DONALD H, RICE, LUCIAN
Format: Article
Language:English
Subjects:
Adenine Nucleotides - metabolism
Adenylyl Cyclases - metabolism
Animals
Cyclic AMP - metabolism
Dogs
Enzyme Activation
Epinephrine - pharmacology
Ethanolamines - pharmacology
Glucagon - pharmacology
Glucosyltransferases - metabolism
Heart - drug effects
Heart - physiology
In Vitro Techniques
Isoproterenol - pharmacology
Myocardium - enzymology
Phosphorylase Kinase - metabolism
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Summary:The purpose of this investigation was to contrast the effect of glucagon and that of epinephrine on the concentration of cyclic adenosine 3′,5′-monophosphate (cyclic AMP), the activity of phosphorylase a and the contractile amplitude of isolated perfused rat hearts. The two drugs were about equally effective except that the maximal augmentation of contractility by epinephrine (5 × 10 moles) was twice that produced by an equivalent dose of glucagon with a fourfold greater increase in cyclic AMP concentration. Combination of large doses of the two drugs caused increases in the cyclic nucleotide considerably greater than those required for maximal phosphorylase activation or associated with a maximal inotropic response. The effects of glucagon also developed more slowly than those of epinephrine. An increase in cyclic AMP was not detectable until after phosphorylase a and contractile amplitude had increased.The beta-receptor-blocking agents dichloroisoproterenol and pronethalol did not block the biochemical responses to glucagon in doses which abolished the epinephrine-induced increases in cyclic AMP and phosphorylase a. These results, along with those obtained by other investigators, indicate that glucagon can elicit the same biochemical responses in intact heart as have been obtained with epinephrine, but by action at a different receptor site.
ISSN:0009-7330
1524-4571
DOI:10.1161/01.RES.26.2.225